One technique for manufacturing pharmaceutical products employs a means wherein core particles are prepared in a fluidized state, a drug (active ingredient) either alone or mixed with an excipient is introduced thereinto, and the drug or mixture coats the surface of the core particles. In such a case, the requirements for the core particles are: 1) they are generally spherical and of a uniform size, and 2) the core particles do not break up during the coating step (i.e., they have a specified mechanical strength).
Organic materials have mainly been used for prior art core particles. For example, there are core particles of crystalline cellulose alone (Patent Document 1), core particles of a sugar alone (Patent Document 2), core particles comprising a sugar and crystalline cellulose (Patent Document 3), core particles comprising a sugar and a starch (Patent Document 4), and core particles using a single substance selected from a group of consisting of a sugar alcohol, vitamin C, and sodium chloride (Patent Document 5).
To stabilize a drug that is unstable in an acid, however, the surfaces of the core particles disclosed in Patent Documents 1 to 4 must be coated with a layer comprising a basic substance (e.g., magnesium carbonate) and an organic binder before being coated with the drug.
In addition, with the core particles of crystalline cellulose alone disclosed in Patent Document 1, if the surfaces of the core particles are not properly coated with the drug, the drug does not completely dissolve in the body because disintegration in the gastrointestinal tract (particularly the stomach) after oral administration requires too much time, and the desired absorption via the gastrointestinal tract cannot be achieved.
Sugar or sodium chloride is used in the core particles of Patent Documents 2 to 5, and therefore the sugar or sodium chloride gets dissolved away by the infiltration of water, shape retention of the particles becomes poor during processing, and therefore sustained release cannot be stably maintained. In addition, if a water-based solvent is used during the coating process, the particles are more likely to cohere to each other and adhere to the container wall of the granulator. Additionally, when such a preparation is administered to diabetic patients, the sugar or salt burden becomes a problem in treating the diabetes.
Furthermore, the core particles of sugar alone disclosed in Patent Document 2 lack hardness, so the particles break up in the coating step and become a powder.
Not only do the core particles comprising sugar and starch disclosed in Patent Document 4 have insufficient hardness, but because sucrose, which has needle-shaped crystals, is used as the sugar, the surface is very uneven resulting in a high degree of friability. Furthermore, it is known that when a reducing sugar is used as the sugar as in Patent Document 4, discoloration may occur due to a chemical reaction if an amino compound or organic acid is used as the active ingredient.
Finally, when an inorganic substance is used as the structural material of core particles such as in Patent Documents 1 to 5, there is a limit to the processing temperature, and processing (drying) requires a long time.    Patent Document 1: Japanese Patent Application Publication No. H7-173050    Patent Document 2: Japanese Patent Application Publication No. H6-205959    Patent Document 3: Japanese Patent No. 3219787    Patent Document 4: Japanese Patent Application Publication No. H9-175999    Patent Document 5: Japanese Patent No. 3447042